Molecular mechanisms of Candida sepsis

Scanning electron micrograph showing C. albicans interacting with epithelial cells. Hyphae penetrate through and between the epithelial cells leading to tissue destruction.
Scanning electron micrograph showing C. albicans interacting with epithelial cells. Hyphae penetrate through and between the epithelial cells leading to tissue destruction.

The most common fungal pathogen of the genus Candida is Candida albicans (C. albicans). During systemic infections, Candida albicans can infect almost all organs, which can cause disregulation of the immune system and organ failure. In the murine model of haematogenously disseminated candidiasis, mice die of progressive sepsis, kidney inflammation and failure, while fungal load declines in all other infected organs without causing pathological alterations. This data suggests that fungal pathogenicity is not only due to damage caused by the fungus, but also due to an inappropriate host response leading to damage caused by immune cells.

In this project, we aim at understanding the molecular mechanisms of sepsis induction triggered by C. albicans by identifying fungal genes, factors or activities which are responsible for or contribute to the organ-specific host responses. We propose that fungal genes exist, which are required for an organ-specific host response which is either protective or non-protective. We will use in vivo transcriptional profiling and large scale C. albicans mutant collection screening to identify such genes. The knowledge of these genes and their role during systemic C.  albicans infection provide new options for antifungal therapies, which are urgently required due to the high mortality rates caused by C. albicans.


Mentrup T, Stumpff-Niggemann AY, Leinung N, Schlosser C, Schubert K, Wehner R, Tunger A, Schatz V, Neubert P, Gradtke AC, Wolf J, Rose-John S, Saftig P, Dalpke A, Jantsch J, Schmitz M, Fluhrer R, Jacobsen ID, Schröder B (2022) Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nat Commun 13(1), 1880.
Ramírez-Zavala B, Krüger I, Dunker C, Jacobsen ID, Morschhäuser J (2022) The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans. PLOS Pathog 18(2), e1010283.
Dunker C, Polke M, Schulze-Richter B, Schubert K, Rudolphi S, Gressler AE, Pawlik T, Prada Salcedo JP, Niemiec MJ, Slesiona-Künzel S, Swidergall M, Martin R, Dandekar T, Jacobsen ID (2021) Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain. Nat Commun 12(1), 3899.
Machata S, Sreekantapuram S, Hünniger K, Kurzai O, Dunker C, Schubert K, Krüger W, Schulze-Richter B, Speth C, Rambach G, Jacobsen ID (2021) Significant differences in host-pathogen interactions between murine and human whole blood. Front Immunol 11, 565869.
Papon N, Naglik JR, Hube B, Goldman GH (2021) Fungal pathogenesis: A new venom. Curr Biol 31(8), R391-R394. (Review)
Fischer J, Walter C, Tönges A, Aleth H, Jordão MJC, Leddin M, Gröning V, Erdmann T, Lenz G, Roth J, Vogl T, Prinz M, Dugas M, Jacobsen ID, Rosenbauer F (2019) Safeguard function of PU.1 shapes the inflammatory epigenome of neutrophils. Nat Immunol 20(5), 546-558.
Beyer R, Jandric Z, Zutz C, Gregori C, Willinger B, Jacobsen ID, Kovarik P, Strauss J, Schüller C (2018) Competition of Candida glabrata against Lactobacillus is Hog1 dependent. Cell Microbiol 20(12), e12943.
Eberl C, Speth C, Jacobsen ID, Hermann M, Hagleitner M, Deshmukh H, Ammann CG, Lass-Flörl C, Rambach G (2018) Candida: Platelet interaction and platelet activity in vitro. J Innate Immun 11(1), 52-62.


These projects are supported by the Center for Sepsis Control and Care (CSCC), a BMBF project (BMBF 01EO1002).